MS-specific Lineage of Oligodendrocytes May Provide New Hints on MS Development

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by Ana Pena PhD |

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oligodendrocytes role in MS

The cells that produce myelin in the brain and spinal cord, called oligodendrocytes, may play an active role in the onset or progression of multiple sclerosis (MS), according to a study combining data from MS mouse models and the human brain.

This discovery supports the idea that in the context of MS, oligodendrocytes could act similarly to immune cells, a finding that may underpin new therapies targeted to these cells, rather than only to the immune system.

The study, “Disease-specific oligodendrocyte lineage cells arise in multiple sclerosis,” was published in the journal Nature Medicine.

Oligodendrocytes are one of the most abundant cell types of the central nervous system (brain and spinal cord), and the ones responsible for producing the myelin sheaths that insulate nerve fibers and allow electrical impulses to be quickly transmitted.

A team led by researchers at the Karolinska Institutet in Sweden have now found that oligodendrocytes, besides being producers of myelin, might be important players in the development of neurological diseases like MS.

Researchers took an in-depth look at the profile of active and silenced genes in spinal cord oligodendrocytes of MS mouse models — namely the experimental autoimmune encephalomyelitis (EAE) model that mimics several aspects of MS.

They analyzed the patterns of gene expression using a recent technique called single-cell RNA sequencing, which delivers a snapshot of the genetic activity of individual cells, providing scientists with clues about their properties and functions.

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Researchers saw that when MS-like disease was induced in mice, a group of oligodendrocytes and their precursor cells appeared, which had a unique pattern of gene expression. Specifically, they shared properties with cells belonging to the immune system.

Importantly, these cells could behave like some immune cells that “ingest” other cells or molecules — a process called phagocytosis — and trigger an immune response against them, known as antigen presentation. These cellular processes take part in the destruction of myelin by the autoimmune response during MS.

Similar to immune cells, the disease-associated oligodendrocyte lineage activated genes are involved in the stimulation of immune responses and immunoprotection. The oligodendrocyte progenitors could also regulate the survival and replication of T-cells, one of the most important immune cell types.

Notably, and in line with the mice findings, the team also identified MS-specific oligodendrocytes in brain samples of MS patients.

“Our study provides a new perspective on how multiple sclerosis might emerge and evolve,” Gonçalo Castelo-Branco, PhD, associate professor at the Karolinska Institutet and senior author of the study, said in a press release.

“Current treatments mainly focus on inhibiting the immune system. But we can now show that the target cells of the immune system in the brain and spinal cord, oligodendrocytes, acquire new properties during disease and might have a higher impact on the disease than previously thought,” Castelo-Branco added. 

These findings suggest that oligodendrocytes may play unexpected roles and actively participate in the disease process as immunomodulators.

“We will now continue with further studies to ascertain the part played by the oligodendrocytes and their progenitor cells in MS,” Castelo-Branco said. “Further knowledge can eventually lead the way to the development of new treatments for the disease.”

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